Aims: Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) affect a large percentage of diabetic people and impact severely on quality of life. As it seems that miRNAs and their variations might play a role in these complications, we investigated whether the rs3746444 SNP in the MIR499A gene could be associated with susceptibility to DPN and/or CAN. Methods: We analyzed 150 participants with type 2 diabetes. DNA was extracted from peripheral blood samples and genotyping was performed by TaqMan genotyping assay. Cardiovascular tests, MNSI-Q and MDNS for neuropathic symptoms and signs, VPT, and thermal thresholds were used for CAN and DPN assessment. We performed a genotype-phenotype correlation analysis. Results: We observed that the GG genotype was associated with a higher risk of developing CAN (P=0.002 and OR=16.08, P=0.0005 and OR=35.02, for early and confirmed CAN, respectively) and DPN (P=0.037 and OR=6.56), after correction for BMI, sex, age, HbA1c and disease duration. Moreover, the GG genotype was associated with worse values of MDNS (P=0.017), VPT (P=0.01), thermal thresholds (P=0.01), and CAN score (P<0.001). A logistic multivariate analysis confirmed that MIR499A GG genotype, disease duration and HbA1c contributed to early CAN (R2=0.26), while the same variables and age contributed to DPN (R2=0.21). With a multiple linear regression, we observed that GG genotype (P=0.001) and disease duration (P=0.035) were the main variables contributing to the CAN score (R2=0.35).Conclusions: We described for the first time that the MIR499A genetic variation could be involved in diabetic neuropathies susceptibility. In particular, patients carrying the rs3746444 GG genotype had a higher risk of CAN development, together with a more severe form of CAN.
Ciccacci, C., Latini, A., Greco, C., Politi, C., D'Amato, C., Lauro, D., et al. (2018). Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes. JOURNAL OF DIABETES AND ITS COMPLICATIONS, 32(1), 11-17.
Tipologia: | Articolo su rivista |
Citazione: | Ciccacci, C., Latini, A., Greco, C., Politi, C., D'Amato, C., Lauro, D., et al. (2018). Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes. JOURNAL OF DIABETES AND ITS COMPLICATIONS, 32(1), 11-17. |
URL: | http://www.sciencedirect.com/science/article/pii/S1056872717303215 |
Altre informazioni significative: | Sono limitate le informazioni su una eventuale predisposizione genetica alla neuropatia diabetica, mentre diventa sempre più rilevante il ruolo dei miRNA nello sviluppo delle complicanze del diabete. Lo studio valuta l'associazione tra il polimorfismo rs3746444 SNP del gene MIR499A e la suscettibilità a sviluppare la neuropatia diabetica nelle sue forme sensitivomotoria e autonomica. Il genotipo GG è risultato associato ad un rischio aumentato di neuropatia diabetica. La relazione è particolarmente evidente per la neuropatia autonomica cardiovascolare. Considerando che il miR-499 è espresso a livello cardiaco e nel nucleo ambiguo, coinvolti entrambi nel circuito di controllo autonomico cardiovascolare, una variazione dell'espressione del miR-499 conseguente al genotipo GG potrebbe ridurre in queste aeree meccanismi di protezione verso il danno metabolico. Lo studio è stato finanziato con un grant Fondazione Roma 2013. |
IF: | Con Impact Factor ISI |
Lingua: | English |
Settore Scientifico Disciplinare: | Settore MED/03 - Genetica Medica Settore MED/13 - Endocrinologia |
Revisione (peer review): | Esperti anonimi |
Tipo: | Articolo |
Rilevanza: | Rilevanza internazionale |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.jdiacomp.2017.10.011 |
Stato di pubblicazione: | Pubblicato |
Data di pubblicazione: | 2018 |
Titolo: | Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes |
Autori: | |
Autori: | Ciccacci, C; Latini, A; Greco, C; Politi, C; D'Amato, C; Lauro, D; Novelli, G; Borgiani, P; Spallone, V |
Appare nelle tipologie: | 01 - Articolo su rivista |
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